The compound (+)-2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-2-oxo-hexyl)-1-isoindolinone, also called pagoclone, is a GABA (gamma amino butyric acid) receptor ligand that is presently being evaluated in human clinical studies for the treatment of generalized anxiety disorder and panic disorder.
The compound 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-5-hydroxy-2-oxohexyl)-1-isoindolinone is a hydroxy metabolite of pagoclone that shows GABA activity and which can be used to treat generalized anxiety disorder and panic disorder. This compound is disclosed and its preparation and the preparation of each enantiomer is shown in U.S. Pat. No. 5,494,915.
U.S. Pat. No. 4,960,779, issued on Oct. 2, 1990, relates to pyrrole derivatives and compositions comprising pyrrole derivatives, including pagoclone, and to methods of producing an anxiolytic, hypnotic, anticonvulsant, antiepileptic or muscle relaxant therapeutic effect that comprises administering a pyrrole derivative.
The present invention is directed to the use of pyrrole derivatives, and specifically pagoclone or a hydroxy metabolite of pagoclone, 2-(7-chloro-1,8-naphthyridine-2-yl)-3-(5-methyl-5-hydroxy-2-oxohexyl)-1-isoindolinone, to treat obsessive-compulsive disorder, acute stress disorder, post traumatic stress disorder, social anxiety disorder, somatization disorder, specific social phobia, premenstrual dysphoric disorder, anxiety associated with a medical condition, adjustment disorder with anxious mood, dysthymia, specific phobia or fibromyalgia.
GABA is a neurotransmitter that acts at GABA receptors. Two primary types of GABA receptors have been identified as GABM and GABAB. GABAA is a GABA-gated chloride ion channel, whereas GABAB is a G-protein coupled receptor. The present invention is primarily concerned with compounds that act on the GABM receptor.